Multifunctional monomers, methods for making multifunctional monomers, polymerizable compostions and products formed thereform

ABSTRACT

The present invention provides multifunctional monomers, including, but not limited to include multifunctional methylene malonate and methylene beta-ketoester monomers; methods for producing the same; and compositions and products formed therefrom. The multifunctional monomers of the invention may be produced by transesterification or by direct synthesis from monofunctional methylene malonate monomers or methylene beta-ketoester monomers. The present invention further compositions and products formed from methylene beta-ketoester monomers of the invention, including monomer-based products (e.g., inks, adhesives, coatings, sealants or reactive molding) and polymer-based products (e.g., fibers, films, sheets, medical polymers, composite polymers and surfactants).

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a 35 U.S.C. §371 National Phase Application ofInternational PCT Patent Application No. PCT/US2012/060830, filed Oct.18, 2012, which application claims the benefit of priority to U.S.Provisional Patent Applications Ser. Nos. 61/549,092 filed Oct. 19,2011; 61/549,104, filed Oct. 19, 2011; and 61/549,152, filed Oct. 19,2011, the contents of each of which in their entirety are herebyincorporated herein by reference.

INCORPORATION BY REFERENCE

All documents cited or referenced herein and all documents cited orreferenced in the herein cited documents, together with anymanufacturer's instructions, descriptions, product specifications, andproduct sheets for any products mentioned herein or in any documentincorporated by reference herein, are hereby incorporated by reference,and may be employed in the practice of the invention.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention relates to multifunctional monomers, to methods ofproducing or synthesizing such monomers, and to the use and applicationof such monomers as commercial products and compositions, including, forexample, monomer-based products (e.g., inks, adhesives, coatings,sealants or reactive molding) and polymer-based products (e.g., fibers,films, sheets, medical polymers, composite polymers and surfactants).

Specific embodiments are directed to multifunctional methylene malonateand methylene beta-ketoester monomers but the principles disclosedherein are relevant to other disubstituted vinyl compounds havingelectron withdrawing groups in the beta position.

2. Background

Methylene malonate monomers, methylene beta-ketoester monomers and theirassociated monomeric and polymeric-based products would be useful inboth industrial (including household) and medical applications. Indeed,unlike many other monomers, these monomers and their products can beproduced via sustainable routes as well as be designed to beenvironmentally benign, biologically benign and as such many of theproducts can be generally regarded as “green.”

Methylene malonate monomers and methylene beta-ketoester monomers havethe potential to form the basis of a large-scale platforms of new rawmaterials for the generation of a wide variety of new chemical products,including inks, adhesives, coatings, sealants, moldings, fibers, films,sheets, medical polymers, composites, surfactants and the like. Whilethe production of monofunctional methylene malonates by variousprocesses has been known for many years, these earlier methods suffersignificant deficiencies that preclude their use in obtaining viablemonomers for commercial exploitation. Such deficiencies in these oldermethods include unwanted polymerization of the monomers during synthesis(e.g., formation of polymers or oligomers or alternative complexes),formation of undesirable side products (e.g., ketals or other latentacid-forming species which impede rapid polymerization), and degradationof the product, insufficient and/or low yields, and ineffective and/orpoorly functioning monomer product (e.g., poor adhesive characteristicsor other functional characteristics), among other problems. The overallpoorer yield, quality, and chemical performance of the monomer productsformed by prior art methods impinges on their practical use in theproduction of the above commercial and industrial products. No viablesolutions to solve the aforementioned problems have yet been proposed,accepted and/or recognized and certainly do not exist currently in theindustry.

In the art, numerous attempts overall have been made to functionalizehighly activated disubstituted vinyl monomers, particularlycyanoacrylates. Cyanoacrylate adhesives are one-part solvent-freeadhesives that cure rapidly through polymerization at room temperature.These adhesives are used in a wide range of applications across variousindustries as a result of their fast and often strong shear strength.Unfortunately, while the cyanoacrylic anionic cure mechanism is facile,poor impact and environmental resistance has vastly limited theirpotential from the broad array of applications that thermosettingsystems allow. For example, thermosetting systems provide the benefitsof cross-linking and allow for a particular physical or chemical traitto be introduced via a multifunctional resin. While attempts have beenmade to produce multifunctional systems for cyanoacrylates they have notbeen met with any commercial success due to poor yields, poor stabilityand high costs. Monomeric systems in the prior art either go through ablocking agent process, the incorporation of a secondary cure or similarprocesses. Multifunctional cyanoacetates converted to cyanoacrylatessimply cannot be cracked to monomer the same way that a monofunctionalcyanoacrylate monomer is made now.

Conversely, while their cure is slower, crosslinked epoxies,polyurethanes, polyesters, silicones polyimides, polyureas and the likeprovide excellent properties but require heat and/or mixing andrelatively long cure times that are energy intensive to polymerize.Multifunctional acrylic systems polymerize quickly, but only at highcatalyst loading, and/or through the use of external energy sources orprimers.

The prior art's attempts at delivering a multifunctional system havebeen met with no commercial success and require long cure times forultimate strength and display poor stability due the use of an allylicfunctionality. The prior art also cannot deliver the wide range ofproperties that a functionalized resin can nor can deliver afunctionality greater than 2 as described in the art.

Accordingly, it would of great utility if multifunctional 1, 2substituted methylene malonates and methylene beta-ketoesters could beproduced not only as reactive monomers but also incorporated as reactivegroups along oligomeric and polymeric backbones. It would be of evenfurther use to not only employ such monomers, oligomers and polymers aspolymerizable molecules, but to also functionalize them for otherpurposes, such as conducting chemistry on the methylene malonates tocreate other functional groups, such as dyes, catalysts, chelatingagents, medicals, anti-fungal agents and the like or to polymerize offof them other monomers to create not a crosslinked system butalternatively a unique copolymer system, such as a polyolefin off ofcertain parts of a polyester.

Also of utility would be the ability to use a process for easilyproducing certain base methylene malonate monomers or methylenebeta-ketoester monomers and then to use a second process to convertthose into more complex, difficult to produce and/or higher molecularweight methylene malonate monomers or methylene beta-ketoester monomers.

Thus, multifunctional monomers, i.e. monomers having two or moremethylene double bonds, would be of interest as they could beselectively functionalized or crosslinked. No viable routes tomultifunctional methylene malonate monomers have yet to be proposed,accepted and/or recognized and certainly do not exist currently in theindustry.

Further, a need exists for methods for synthesizing methylene malonatemonomers and methylene beta-ketoester monomers and others that arecapable of being viably used in commercial and industrial applications.

SUMMARY OF THE INVENTION

The purpose and advantages of the present invention will be set forth inand shall be apparent from the description that follows. Additionaladvantages of the invention will be realized and attained by the methodsand systems particularly pointed out in the written description andclaims hereof, as well as from the appended drawings.

In one aspect, the invention provides a multifunctional monomer havingthe formula:

wherein:

each instance of R¹ and R² are independently C₁-C₁₅ alkyl, C₂-C₁₅alkenyl, halo-(C₁-C₁₅ alkyl), C₃-C₆ cycloalkyl, halo-(C₃-C₆ cycloalkyl),heterocyclyl, heterocyclyl-(C₁-C₁₅ alkyl), aryl, aryl-(C1-C15 alkyl),heteroaryl or heteroaryl-(C₁-C₁₅ alkyl), or alkoxy —(C1-15 alkyl), eachof which may be optionally substituted by C₁-C₁₅ alkyl, halo-(C₁-C₁₅alkyl), C₃-C₆ cycloalkyl, halo-(C₃-C₆ cycloalkyl), heterocyclyl,heterocyclyl-(C₁-C₁₅ alkyl), aryl, aryl —(C₁-C₁₅ alkyl), heteroaryl,C₁-C₁₅ alkoxy, C₁-C₁₅ alkylthio, hydroxyl, nitro, azido, cyano, acyloxy,carboxy, or ester;

-[A]- represents —(CR^(A)R^(B))_(n)—,—(CR^(A)R^(B))_(n)—O(C═O)—(CH₂)₁₋₁₅—(C═O)O—(CR^(A)R^(B))_(n)—,—(CH₂)_(n)—[CY]—(CH₂)_(n), a polybutadienyl linking group, apolyethylene glycol linking group, a polyether linking group, apolyurethane linking group, an epoxy linking group, a polyacryliclinking group, or a polycarbonate linking group;

each instance of R^(A) or R^(B) is independently H, C₁-C₁₅ alkyl, C₂-C₁₅alkenyl, a moiety represented by the formula:

or

wherein:

-   -   -L- is a linking group selected from the group consisting of        alkylene, alkenylene, haloalkylene, cycloalkylene,        cycloalkylene, heterocyclylene, heterocyclyl alkylene,        aryl-alkylene, heteroarylene or heteroaryl-(alkylene), or        alkoxy-(alkylene), each of which may be optionally branched and        each of which may be optionally substituted by alkyl, haloalkyl,        cycloalkyl, halo cycloalkyl, heterocyclyl, heterocyclyl-(alkyl),        aryl, aryl-(alkyl), heteroaryl, C₁-C₁₅ alkoxy, C₁-C₁₅ alkylthio,        hydroxyl, nitro, azido, cyano, acyloxy, carboxy, ester, each of        which may be optionally branched;    -   R³ is independently selected from the group defined in R² above;        and    -   R⁴ is alkyl, alkenyl, haloalkyl, cycloalkyl, halo cycloalkyl,        heterocyclyl, heterocyclyl alkyl), aryl-(alkyl), heteroaryl or        heteroaryl-(alkyl), or alkoxy-(alkyl), each of which may be        optionally branched and each of which may be optionally        substituted by alkyl, haloalkyl), cycloalkyl, halo cycloalkyl,        heterocyclyl, heterocyclyl-(alkyl), aryl, aryl-(alkyl),        heteroaryl, C₁-C₁₅ alkoxy, C₁-C₁₅ alkylthio, hydroxyl, nitro,        azido, cyano, acyloxy, carboxy, ester, each of which may be        optionally branched;

—[CY]— represents an alkyl, alkenyl, haloalkyl, cycloalkyl, halocycloalkyl, heterocyclyl, heterocyclyl alkyl), aryl-(alkyl), heteroarylor heteroaryl-(alkyl), or alkoxy-(alkyl) group

each instance of n is independently an integer from 1 to 25; and

each instance of Q represents —O— or a direct bond.

In another aspect, the invention provides a multifunctional monomerhaving the formula:

wherein:

each instance of R¹ and R² are independently C₁-C₁₅ alkyl, C₂-C₁₅alkenyl, halo-(C₁-C₁₅ alkyl), C₃-C₆ cycloalkyl, halo-(C₃-C₆ cycloalkyl),heterocyclyl, heterocyclyl-(C₁-C₁₅ alkyl), aryl, aryl-(C1-C15 alkyl),heteroaryl or heteroaryl-(C₁-C₁₅ alkyl), or alkoxy —(C1-15 alkyl), eachof which may be optionally substituted by C₁-C₁₅ alkyl, halo-(C₁-C₁₅alkyl), C₃-C₆ cycloalkyl, halo-(C₃-C₆ cycloalkyl), heterocyclyl,heterocyclyl-(C₁-C₁₅ alkyl), aryl, aryl —(C₁-C₁₅ alkyl), heteroaryl,C₁-C₁₅ alkoxy, C₁-C₁₅ alkylthio, hydroxyl, nitro, azido, cyano, acyloxy,carboxy, or ester;

-[A]- represents —(CR^(A)R^(B))_(n)—,—(CR^(A)R^(B))_(n)—O(C═O)—(CH₂)₁₋₁₅—(C═O)O—(CR^(A)R^(B))_(n)—,—(CH₂)_(n)—[CY]—(CH₂)_(n), a polybutadienyl linking group, apolyethylene glycol linking group, a polyether linking group, apolyurethane linking group, an epoxy linking group, a polyacryliclinking group, or a polycarbonate linking group;

each instance of R^(A) or R^(B) is independently H, C₁-C₁₅ alkyl, C₂-C₁₅alkenyl, a moiety represented by the formula:

wherein:

-   -   -L- is a linking group selected from the group consisting of        alkylene, alkenylene, haloalkylene, cycloalkylene,        cycloalkylene, heterocyclylene, heterocyclyl alkylene,        aryl-alkylene, heteroarylene or heteroaryl-(alkylene), or        alkoxy-(alkylene), each of which may be optionally branched and        each of which may be optionally substituted by alkyl, haloalkyl,        cycloalkyl, halo cycloalkyl, heterocyclyl, heterocyclyl-(alkyl),        aryl, aryl-(alkyl), heteroaryl, C₁-C₁₅ alkoxy, C₁-C₁₅ alkylthio,        hydroxyl, nitro, azido, cyano, acyloxy, carboxy, ester, each of        which may be optionally branched;    -   R³ is independently selected from the group defined in R² above;        and    -   R⁴ is alkyl, alkenyl, haloalkyl, cycloalkyl, halo cycloalkyl,        heterocyclyl, heterocyclyl alkyl), aryl-(alkyl), heteroaryl or        heteroaryl-(alkyl), or alkoxy-(alkyl), each of which may be        optionally branched and each of which may be optionally        substituted by alkyl, haloalkyl), cycloalkyl, halo cycloalkyl,        heterocyclyl, heterocyclyl-(alkyl), aryl, aryl-(alkyl),        heteroaryl, C₁-C₁₅ alkoxy, C₁-C₁₅ alkylthio, hydroxyl, nitro,        azido, cyano, acyloxy, carboxy, ester, each of which may be        optionally branched;

—[CY]— represents an alkyl, alkenyl, haloalkyl, cycloalkyl, halocycloalkyl, heterocyclyl, heterocyclyl alkyl), aryl-(alkyl), heteroarylor heteroaryl-(alkyl), or alkoxy-(alkyl) group

n is an integer from 1 to 25;

m is an integer from 1 to 25;

each instance of Q represents —O— or a direct bond.

In still another aspect, the invention provides a method for making amultifunctional methylene malonate monomer. The method comprises:

-   -   (a) reacting a sufficient amount of at least one first methylene        malonate monomer with a sufficient amount of a diol, a polyol or        a polymeric resin having at least two hydroxyl groups in the        presence of a catalyst, under suitable reaction conditions and        sufficient time, to form a reaction complex; and    -   (b) recovering multifunctional methylene malonate monomer from        the reaction complex.

In certain embodiments, the reacting step (a) is performed at roomtemperature and at atmospheric pressure. In other embodiments, thereacting step (a) is performed at elevated temperature and atatmospheric pressure. In still other embodiments, the reacting step (a)is performed at room temperature and under vacuum. In yet otherembodiments, the reacting step (a) is performed at elevated temperatureand under vacuum.

In yet another aspect, the invention provides a method of making amultifunctional beta-ketoester monomer comprising:

-   -   (a) reacting a sufficient amount of at least one first methylene        beta-ketoester monomer with a sufficient amount of a diol, a        polyol or a polymeric resin having at least two hydroxyl groups        in the presence of a catalyst, under suitable reaction        conditions and sufficient time, to form a reaction complex;    -   (b) recovering multifunctional methylene beta-ketoester monomer        from the reaction complex.

In still another aspect, the invention provides a method of making amultifunctional methylene malonate monomer comprising:

-   -   (a) reacting a malonic acid ester or a malonic acid chloride        with a diol, a polyol, or a polymeric resin comprising at least        two hydroxyl groups to form a multifunctional malonic acid        ester;    -   (b) reacting the multifunctional malonic acid ester formed in        step (a) with a source of formaldehyde; optionally in the        presence of an acidic or basic catalyst; and optionally in the        presence of an acidic or non-acidic solvent; and optionally in        the presence of an acid scavenger to form a reaction complex;        and    -   (c) recovering multifunctional methylene malonate monomer from        the reaction complex.

In certain embodiments, utilizing a malonic acid ester, the malonic acidester has the formula:

wherein R and R′ are independently C₁-C₁₅ alkyl, C₂-C₁₅ alkenyl,halo-(C₁-C₁₅ alkyl), C₃-C₆ cycloalkyl, halo-(C₃-C₆ cycloalkyl),heterocyclyl, heterocyclyl-(C₁-C₁₅ alkyl), aryl, aryl-(C1-C15 alkyl),heteroaryl or heteroaryl-(C₁-C₁₅ alkyl), or alkoxy —(C1-15 alkyl), eachof which may be optionally substituted by C₁-C₁₅ alkyl, halo-(C₁-C₁₅alkyl), C₃-C₆ cycloalkyl, halo-(C₃-C₆ cycloalkyl), heterocyclyl,heterocyclyl-(C₁-C₁₅ alkyl), aryl, aryl —(C₁-C₁₅ alkyl), heteroaryl,C₁-C₁₅ alkoxy, C₁-C₁₅ alkylthio, hydroxyl, nitro, azido, cyano, acyloxy,carboxy, or ester.

In certain embodiments, the multifunctional methylene malonates and themultifunctional methylene beta-ketoester monomers formed according tothe methods disclosed herein are capable of bonding glass to a substratein less than about 90 seconds, less than about 60 seconds, less thanabout 30 seconds or less than about 15 seconds.

In other embodiments, the multifunctional methylene malonates and themultifunctional methylene beta-ketoester monomers formed according tothe methods disclosed herein are capable of bonding polycarbonate to asubstrate in less than about 90 seconds, less than about 60 seconds,less than about 45 seconds or less than about 30 seconds.

In exemplary embodiments, the multifunctional methylene malonates andthe multifunctional methylene beta-ketoester monomers formed accordingto the methods disclosed herein are amenable to anionic polymerization.

In yet other embodiments, said composition remains stable at 25° C. andat atmospheric pressure for more than 10 days, more than 15 days, morethan 20 days, more than 25 days or more than 30 days. In still yet otherembodiments, said composition remains stable at 82° C. and atatmospheric pressure for more than about 2 hours, more than about 3hours, or more than about 4 hours.

In certain embodiments, the monomers and polymers of the invention areuseful in products, including, but not limited to, adhesives, coatingcompositions and sealants. Other exemplary products obtained frommultifunctional methylene malonate monomers or methylene beta-ketoestermonomers include thermal barrier coatings, textile fibers,water-treatment polymers, ink carriers, paint carrier, packaging film,moldings, medical polymer, a polymer film, a polymer fiber, and apolymer sheet.

In certain embodiments, the products are formulated to include acidicstabilizers, free radical stabilizers, sequestering agents, cureaccelerators, rheology modifiers, plasticizing agents, thixotropicagents, natural rubbers, synthetic rubbers, filler agents, reinforcingagents, plasticizers, or any combination thereof.

In certain embodiments, the product is stable for at least one year.

BRIEF DESCRIPTION OF THE DRAWINGS

So that those having ordinary skill in the art to which the subjectinvention pertains will more readily understand how to make and use theinvention as described herein, preferred embodiments thereof will bedescribed in detail below, with reference to the drawings, wherein:

FIGS. 1 and 2 depict NMR spectra demonstrating evidence of amultifunctional monomer reaction product formed by thetransesterification of diethyl methylene malonate (DEMM) and1,6-hexanediol (HD).

FIGS. 3, 4 and 5 depict NMR spectra demonstrating evidence of amultifunctional monomer reaction product formed by thetransesterification of DEMM and cyclohexanedimethanol (CHDM).

FIGS. 6 and 7 depict NMR spectra demonstrating evidence of amultifunctional monomer reaction product formed by thetransesterification of DEMM and poly-tetrahydrofuron (poly-THF).

FIGS. 8 and 9 depict NMR spectra demonstrating evidence of amultifunctional monomer reaction product formed by thetransesterification of DEMM and 1,8-octanediol.

FIGS. 10 and 11 depict NMR spectra demonstrating evidence of amultifunctional monomer reaction product formed by thetransesterification of DEMM and 1,10-decanediol.

FIGS. 12 and 13 depict NMR spectra demonstrating evidence of amultifunctional monomer reaction product formed by thetransesterification of DEMM and trimethylolpropane.

FIGS. 14 and 15 depict mass spectroscopy data demonstrating evidence ofa multifunctional monomer reaction product formed by thetransesterification of DEMM and 1,6-hexanediol.

FIGS. 16 and 17 depict NMR spectra demonstrating evidence of amultifunctional monomer reaction product formed by thetransesterification of DEMM and 1,3-benzene dimethanol.

DESCRIPTION OF THE INVENTION

Overview

The present invention provides novel multifunctional methylene malonatemonomers and multifunctional beta-ketoester monomers, methods ofsynthesis thereof, and formulated products and polymers.

Definitions

Unless defined otherwise, all technical and scientific terms used hereinhave the meaning commonly understood by a person skilled in the art towhich this invention belongs. The following references provide one ofskill with a general definition of many of the terms used in thisinvention: Singleton et al., Dictionary of Microbiology and MolecularBiology (2nd ed. 1994); The Cambridge Dictionary of Science andTechnology (Walker ed., 1988); The Glossary of Genetics, 5th Ed., R.Rieger et al. (eds.), Springer Verlag (1991); and Hale & Marham, TheHarper Collins Dictionary of Biology (1991). As used herein, thefollowing terms have the meanings ascribed to them below, unlessspecified otherwise.

As used herein, the term “methylene malonate” refers to a compoundhaving the core formula —O—C(O)—C(═CH₂)—C(O)—O—.

As used here, the term “malonic acid ester” refers to a compound havingthe core formula —O—C(O)—CH₂—C(O)—O—.

As used herein, the term “monofunctional” refers to a malonic acid esteror a methylene malonate having only one core formula.

As used herein, the term “difunctional” refers to a malonic acid esteror a methylene malonate having two core formulas.

As used herein, the term “multifunctional” refers to refers to a malonicacid ester or a methylene malonate having more than one core formulas.Thus the term “difunctional” is encompassed within the term“multifunctional.”

As used herein, the term “reaction complex” refers to the materialswhich result after the initial reaction step(s) for each scheme. Incertain embodiments, the “reaction complex” refers to the materials ofthe reaction prior to the isolation of product. Such reaction complexesmay comprise, without limitation, multifunctional methylene malonatemonomers, oligomeric complexes, irreversible complex impurities,starting materials, or latent acid-forming impurities.

As used herein, the term “reaction vessel” refers to any container inwhich the reactants, solvents, catalysts or other materials may becombined for reaction. Such reaction vessels can be made of any materialknown to one of skill in the art such as metal, ceramic or glass.

As used herein, the term “recovering” or “obtaining” or “isolating” asin “isolating the multifunctional methylene malonate monomer,” refers tothe removal or collection of the monomer from the reaction complex by amethod described herein, or understood by those having skill in the art.As used herein, “recovering” or “isolating” does not necessarily implythat a reaction product has been obtained in a substantially pure form.

As used herein, the term “latent acid-forming impurities” or “latentacid-forming impurity” refers to any impurity that, if present alongwith the recovered methylene malonate monomer, will with time beconverted to an acid. The acid formed from these impurities tends toresult in overstabilization of the multifunctional methylene malonatemonomer, thereby reducing the overall quality and reactivity of themonomer.

As used herein, the term “ketal” refers to molecule having a ketalfunctionality; i.e. a or molecule containing a carbon bonded to two —ORgroups, where O is oxygen and R represents any alkyl group.

As used herein the term “substantial absence” as in “substantial absenceof acidic solvent” refers to a reaction mixture which comprises lessthan 1% by weight of the particular component as compared to the totalreaction mixture. In certain embodiments, a “substantial absence” refersto less than 0.7%, less than 0.5%, less than 0.4% m less than 0.3%, lessthan 0.2% or less than 0.1% by weight of the of the particular componentas compared to the total reaction mixture. In certain other embodiments,a “substantial absence” refers to less than 1.0%, less than 0.7%, lessthan 0.5%, less than 0.4% m less than 0.3%, less than 0.2% or less than0.1% by volume of the of the particular component as compared to thetotal reaction mixture.

As used herein, the term “stabilized,” e.g., in the context of“stabilized” molecules of the invention or compositions comprising same,refers to the tendency of the molecules of the invention (or theircompositions) to substantially not polymerize with time, tosubstantially not harden, form a gel, thicken, or otherwise increase inviscosity with time, and/or to substantially show minimal loss in curespeed (i.e., cure speed is maintained) with time as compared to similarcompositions that are not stabilized.

As used herein, the term “shelf-life,” e.g., as in the context of themolecules of the invention having an improved “shelf-life,” refers tothe molecules of the invention which are stabilized for a given periodof time, e.g., 1 month, 6 months, or even 1 year or more.

Multifunctional Monomers

In one aspect, the invention provides a multifunctional monomer havingthe formula:

wherein:

each instance of R¹ and R² are independently C₁-C₁₅ alkyl, C₂-C₁₅alkenyl, halo-(C₁-C₁₅ alkyl), C₃-C₆ cycloalkyl, halo-(C₃-C₆ cycloalkyl),heterocyclyl, heterocyclyl-(C₁-C₁₅ alkyl), aryl, aryl-(C1-C15 alkyl),heteroaryl or heteroaryl-(C₁-C₁₅ alkyl), or alkoxy —(C1-15 alkyl), eachof which may be optionally substituted by C₁-C₁₅ alkyl, halo-(C₁-C₁₅alkyl), C₃-C₆ cycloalkyl, halo-(C₃-C₆ cycloalkyl), heterocyclyl,heterocyclyl-(C₁-C₁₅ alkyl), aryl, aryl-(C1-C15 alkyl), heteroaryl,C₁-C₁₅ alkoxy, C1-C15 alkylthio, hydroxyl, nitro, azido, cyano, acyloxy,carboxy, or ester;

-[A]- represents —(CR^(A)R^(B))_(n)—,—(CR^(A)R^(B))_(n)—O(C═O)—(CH₂)₁₋₁₅—(C═O)O—(CR^(A)R^(B))_(n)—,—(CH₂)_(n)—[CY]—(CH₂)_(n), a polybutadienyl linking group, apolyethylene glycol linking group, a polyether linking group, apolyurethane linking group, an epoxy linking group, a polyacryliclinking group, or a polycarbonate linking group;

each instance of R^(A) or R^(B) is independently H, C₁-C₁₅ alkyl, C₂-C₁₅alkenyl, a moiety represented by the formula:

wherein:

-   -   -L- is a linking group selected from the group consisting of        alkylene, alkenylene, haloalkylene, cycloalkylene,        cycloalkylene, heterocyclylene, heterocyclyl alkylene,        aryl-alkylene, heteroarylene or heteroaryl-(alkylene), or        alkoxy-(alkylene), each of which may be optionally branched and        each of which may be optionally substituted by alkyl, haloalkyl,        cycloalkyl, halo cycloalkyl, heterocyclyl, heterocyclyl-(alkyl),        aryl, aryl-(alkyl), heteroaryl, C₁-C₁₅ alkoxy, C₁-C₁₅ alkylthio,        hydroxyl, nitro, azido, cyano, acyloxy, carboxy, ester, each of        which may be optionally branched;    -   R³ is independently selected from the group defined in R² above;        and    -   R⁴ is alkyl, alkenyl, haloalkyl, cycloalkyl, halo cycloalkyl,        heterocyclyl, heterocyclyl alkyl), aryl-(alkyl), heteroaryl or        heteroaryl-(alkyl), or alkoxy-(alkyl), each of which may be        optionally branched and each of which may be optionally        substituted by alkyl, haloalkyl), cycloalkyl, halo cycloalkyl,        heterocyclyl, heterocyclyl-(alkyl), aryl, aryl-(alkyl),        heteroaryl, C₁-C₁₅ alkoxy, C₁-C₁₅ alkylthio, hydroxyl, nitro,        azido, cyano, acyloxy, carboxy, ester, each of which may be        optionally branched;

—[CY]— represents an alkyl, alkenyl, haloalkyl, cycloalkyl, halocycloalkyl, heterocyclyl, heterocyclyl alkyl), aryl-(alkyl), heteroarylor heteroaryl-(alkyl), or alkoxy-(alkyl) group

each instance of n is independently an integer from 1 to 25; and

each instance of Q represents —O— or a direct bond.

In another aspect, the invention provides a multifunctional monomerhaving the formula:

wherein:

each instance of R¹ and R² are independently C₁-C₁₅ alkyl, C₂-C₁₅alkenyl, halo-(C₁-C₁₅ alkyl), C₃-C₆ cycloalkyl, halo-(C₃-C₆ cycloalkyl),heterocyclyl, heterocyclyl-(C₁-C₁₅ alkyl), aryl, aryl-(C1-C15 alkyl),heteroaryl or heteroaryl-(C₁-C₁₅ alkyl), or alkoxy —(C1-15 alkyl), eachof which may be optionally substituted by C₁-C₁₅ alkyl, halo-(C₁-C₁₅alkyl), C₃-C₆ cycloalkyl, halo-(C₃-C₆ cycloalkyl), heterocyclyl,heterocyclyl-(C₁-C₁₅ alkyl), aryl, aryl —(C₁-C₁₅ alkyl), heteroaryl,C₁-C₁₅ alkoxy, C₁-C₁₅ alkylthio, hydroxyl, nitro, azido, cyano, acyloxy,carboxy, or ester;

-[A]- represents —(CR^(A)R^(B))_(n)—,—(CR^(A)R^(B))_(n)—O(C═O)—(CH₂)₁₋₁₅—(C═O)O—(CR^(A)R^(B))_(n)—,—(CH₂)_(n)—[CY]—(CH₂)_(n), a polybutadienyl linking group, apolyethylene glycol linking group, a polyether linking group, apolyurethane linking group, an epoxy linking group, a polyacryliclinking group, or a polycarbonate linking group;

each instance of R^(A) or R^(B) is independently H, C₁-C₁₅ alkyl, C₂-C₁₅alkenyl, a moiety represented by the formula:

wherein:

-   -   -L- is a linking group selected from the group consisting of        alkylene, alkenylene, haloalkylene, cycloalkylene,        cycloalkylene, heterocyclylene, heterocyclyl alkylene,        aryl-alkylene, heteroarylene or heteroaryl-(alkylene), or        alkoxy-(alkylene), each of which may be optionally branched and        each of which may be optionally substituted by alkyl, haloalkyl,        cycloalkyl, halo cycloalkyl, heterocyclyl, heterocyclyl-(alkyl),        aryl, aryl-(alkyl), heteroaryl, C₁-C₁₅ alkoxy, C₁-C₁₅ alkylthio,        hydroxyl, nitro, azido, cyano, acyloxy, carboxy, ester, each of        which may be optionally branched;    -   R³ is independently selected from the group defined in R² above;        and    -   R⁴ is alkyl, alkenyl, haloalkyl, cycloalkyl, halo cycloalkyl,        heterocyclyl, heterocyclyl alkyl), aryl-(alkyl), heteroaryl or        heteroaryl-(alkyl), or alkoxy-(alkyl), each of which may be        optionally branched and each of which may be optionally        substituted by alkyl, haloalkyl), cycloalkyl, halo cycloalkyl,        heterocyclyl, heterocyclyl-(alkyl), aryl, aryl-(alkyl),        heteroaryl, C₁-C₁₅ alkoxy, C₁-C₁₅ alkylthio, hydroxyl, nitro,        azido, cyano, acyloxy, carboxy, ester, each of which may be        optionally branched;

—[CY]— represents an alkyl, alkenyl, haloalkyl, cycloalkyl, halocycloalkyl, heterocyclyl, heterocyclyl alkyl), aryl-(alkyl), heteroarylor heteroaryl-(alkyl), or alkoxy-(alkyl) group

n is an integer from 1 to 25;

m is an integer from 1 to 25;

each instance of Q represents —O— or a direct bond.

In certain embodiments, the invention provides multifunctional monomerhaving the formula:

wherein:

each instance of R¹ and R² are independently C₁-C₁₅ alkyl, C₂-C₁₅alkenyl, halo-(C₁-C₁₅ alkyl), C₃-C₆ cycloalkyl, halo-(C₃-C₆ cycloalkyl),heterocyclyl, heterocyclyl-(C₁-C₁₅ alkyl), aryl, aryl-(C1-C15 alkyl),heteroaryl or heteroaryl-(C₁-C₁₅ alkyl), or alkoxy —(C1-15 alkyl), eachof which may be optionally substituted by C₁-C₁₅ alkyl, halo-(C₁-C₁₅alkyl), C₃-C₆ cycloalkyl, halo-(C₃-C₆ cycloalkyl), heterocyclyl,heterocyclyl-(C₁-C₁₅ alkyl), aryl, aryl —(C₁-C₁₅ alkyl), heteroaryl,C₁-C₁₅ alkoxy, C₁-C₁₅ alkylthio, hydroxyl, nitro, azido, cyano, acyloxy,carboxy, or ester;

[A] represents —(CH₂)_(n)—,—(CH₂)_(n)—O(C═O)—(CH₂)₁₋₁₅—(C═O)O—(CH₂)_(n)—, (CH₂)_(n)—[CY]—(CH₂)_(n),a polybutadienyl linking group, a polyethylene glycol linking group, apolyether linking group, a polyurethane linking group, an epoxy linkinggroup, a polyacrylic linking group, or a polycarbonate linking group;

[CY] represents an alkyl, alkenyl, haloalkyl, cycloalkyl, halocycloalkyl, heterocyclyl, heterocyclyl alkyl), aryl-(alkyl), heteroarylor heteroaryl-(alkyl), or alkoxy-(alkyl) group;

each instance of n is independently an integer from 1 to 25; and

each instance of Q represents —O— or a direct bond.

In other embodiments, the invention provides a multifunctional monomerhaving the formula:

wherein:

each instance of R¹ and R² are independently C₁-C₁₅ alkyl, C₂-C₁₅alkenyl, halo-(C₁-C₁₅ alkyl), C₃-C₆ cycloalkyl, halo-(C₃-C₆ cycloalkyl),heterocyclyl, heterocyclyl-(C₁-C₁₅ alkyl), aryl, aryl-(C1-C15 alkyl),heteroaryl or heteroaryl-(C₁-C₁₅ alkyl), or alkoxy —(C₁₋₁₅ alkyl), eachof which may be optionally substituted by C₁-C₁₅ alkyl, halo-(C₁-C₁₅alkyl), C₃-C₆ cycloalkyl, halo-(C₃-C₆ cycloalkyl), heterocyclyl,heterocyclyl-(C₁-C₁₅ alkyl), aryl, aryl —(C₁-C₁₅ alkyl), heteroaryl,C₁-C₁₅ alkoxy, C₁-C₁₅ alkylthio, hydroxyl, nitro, azido, cyano, acyloxy,carboxy, or ester;

[A] represents a linking group derived from C₁-C₁₂ alkyl diol, anyisomer of cyclohexane dimethanol, polybutyl THF, or trimethylolpropane;each instance of Q represents —O— or a direct bond.

In still other embodiments, the invention provides a multifunctionalmonomer having the formula:

wherein:

each instance of R¹ and R² are independently C₁-C₆ alkyl or aryl;

-[A]- represents C₁-C₁₅ alky, or C₃-C₆ cycloalkyl; and

each instance of Q represents —O— or a direct bond.

Synthetic Methods

The present invention provides two routes to the synthesis ofmultifunctional methylene malonate (MMM) monomers. In specificembodiments, the methods, inter alfa, (a) significantly reduces oreliminates the formation of alternative products, (b) significantlyreduces or eliminates unwanted consumption of MMM monomers and (c)significantly reduces or eliminates the degradation of MMM monomers inthe reaction and subsequent recovery and storage stages. Also disclosedis a route to synthesize multifunctional methylene beta-ketoester (MBK)monomers. Collectively the MMM and MBK are referred to as“multifunctional monomers.”

Overall, the chemistry disclosed herein for synthesizing themultifunctional monomers solves the problem of providing multiple highlyreactive double bonds into a molecule for subsequent reaction.Specifically, the incorporation of more than one methylene malonate orbeta-ketoester functionality, optionally also incorporating a specificbackbone functionality, for polymerization that leads to crosslinking orside polymerizations can:

-   -   1. Improve solvent resistance or compatibility;    -   2. Improve or reduce thermal resistance;    -   3. Incorporate specific performance characteristics, such as        toughness, impact resistance, certain chemical resistances,        optical properties, property combinations, and the like;    -   4. Incorporate less expensive backbone raw materials;    -   5. Increase and/or accelerate cure speed and property build; and    -   6. Increase or decrease adhesion.

Thus, products which can be formed are wide ranging, from adhesives,coatings, sealants, inks and binders to optical polymers, engineeringpolymers, composites, reaction injection molded polymers, and waterswellable polymers. Also, the specific products made, include assembledobjects, rigid and flexible laminates, printed materials and surfaces,composite articles, water and solvent absorbent plastics and devices,textiles, films, sheet goods, construction materials, and so on.

Additionally, reaction with the incorporated methylene double bonds canfacilitate incorporating additional chemical functionality, for examplevia Michael additions:

1. Reactions to incorporate dyes;

2. Reactions to incorporate medicants;

3. Reactions to incorporate anti-fungal agents or similar;

4. Reactions to incorporate catalysts or other functionalities, such asacid groups; and

5. Reactions to incorporate chelating or flocculating agents.

Thus, imagined products are wide ranging, as above, with the additionsof heterogeneous or polymer bound catalysts, medicants, and antifungalagents or the like. Also enabled are predyed textile fibers, composites,plastics and reactive formulations, as well as compostable andrecyclable water swellable polymers.

Any condensation reaction where the initial functional group and/or thepost reaction remaining functional groups do not react readily with thedisubstituted vinyl functionality may be utilized. Accordingly, acidcatalyzed systems and neutral or acidic functional groups are preferred.Specifically, methylene malonate esters and acids as well as methylenebeta-ketoester monomers may be coupled with hydroxyl functionalchemicals via direct or trans-esterification.

Heterogeneous catalysts are preferred as they facilitate separation fromthe typically acidic catalysts that if left in the product couldunacceptably inhibit polymerization. Of several catalyst systems triedto date, the enzyme catalyst is showing the best results for making andisolating a polymerizable composition of the multifunctional monomers.

The trans-esterification synthesis route is generally carried out inexcess monofunctional methylene malonate (or monofunctionalbeta-ketoester) without the need for solvent.

Synthesis processes for monofunctional methylene malonates may be foundin PCT International Applications filed Oct. 19, 2011, claiming priorityto U.S. Provisional Application Ser. Nos. 61/405,029, filed Oct. 20,2010; 61/405,033, filed Oct. 20, 2010; 61/405,049, filed Oct. 20, 2010;61/405,056, filed Oct. 20, 2010; 61/405,078, filed Oct. 20, 2010;61/523,311, filed Aug. 13, 2011; and 61/523,705, filed Aug. 15, 2011,the entire contents each of which are incorporated herein by referencein their entireties.

It is envisioned that methods disclosed herein can be utilized toconvert simpler methylene malonate monomers or beta-ketoester monomersinto more complex, difficult to produce and/or higher molecular weightmonofunctional methylene malonate monomers or methylene beta-ketoestermonomers.

A second method for functionalization is illustrated by using the latterdescribed methods and stoichiometry to introduce an additionalfunctionality, such as a hydroxyl group, for derivitization. By example,a diol may be reacted in excess with a methylene malonate or a methylenebeta-ketoester to produce a hydroxyl terminated molecule. Specifically,we have reacted an excess of butane diol with diethyl methylene malonateto produce such a molecule. A polymer or resin or larger molecule maythen be created by, for example, reacting the new diol with an acidchloride, a lactone, an epoxy, a diacid or an anhydride or similarmolecule to produce a higher molecular weight molecule, oligomer orpolymer containing methylene malonates in the backbone. Even further,one could add in non-malonate functional acid chlorides, lactones,epoxies, diacids or anhydrides or similar molecules to control thespecific amount of incorporated disubstituted vinyl monomer.

Direct Knoevenagel Synthesis

The Knoevenagel reaction with formaldehyde for the synthesis ofmonofunctional methylene malonate monomers has been previouslydescribed. The typical Knoevenagel reaction combines one mole of amalonic acid ester (e.g., a mono- or disubstituted malonate) and onemole of formaldehyde to form, via catalytic (chemical reaction) actionin the presence of a basic catalyst and an acidic solvent, a methylenemalonate monomer, as depicted in Schematic 1, below.

Certain exemplary embodiments contemplate the use of a modifiedKnoevenagel Synthesis for formation of MMM monomers. As exemplifiedbelow, a malonic acid ester or a malonic acid chloride is reacted with alinking group (a diol, a polyol, an aliphatic alcohol comprising two ormore hydroxyl groups or a polymeric resin comprising two or morehydroxyl group, a polybutadienyl linking group, or a polyethylene glycollinking group) to form a multifunctional malonic acid ester.

The multifunctional malonic acid ester is then reacted with a source offormaldehyde; optionally in the presence of an acidic or basic catalyst;and optionally in the presence of an acidic or non-acidic solvent, toform a reaction complex from which the MMM monomer can be isolated.

In certain embodiments of the invention, the reacting step is performedat about 60° C. to about 130° C. Depending on the source of formaldehydeused, the reaction step can be performed at about 20° C. to about 50°C., or about 30° C. to about 40° C. In still other instances,particularly, though not limited to, instances when the source offormaldehyde is a gas, the reaction step can be performed at about 0° C.to about 25° C.—provided the reaction mixture is a liquid at suchtemperatures.

Other exemplary embodiments contemplate the transesterification ofmonofunctional methylene malonate monomers and monofunctional methylenebeta-ketoester monomers for the formation of multifunctional monomers.As illustrated below, a monofunctional methylene malonate monomer isreacted with a diol, polyol, or polymeric resin having two or morehydroxyl groups, to form a multifunctional methylene malonate monomer. Asimilar reaction scheme may be utilized with a monofunctional methylenebeta-ketoester to form a multifunctional methylene beta-ketoestermonomer.

It is envisioned that for the transesterification reaction describedabove, one could utilize any material having a reactive —OH groupincluding oligomeric and polymeric alcohols, and alcohols which wouldresults in polybutadienyl terminal or linking groups, a polyethyleneglycol terminal or linking groups, a polyether terminal or linkinggroups, a polyurethane terminal or linking groups, an epoxy terminal orlinking groups, a polyacrylic terminal or linking groups, or apolycarbonate terminal or linking groups. Such alcohols may be smallmolecules (linear or branched); polymeric, oligomeric, or resinous. Inthe instance of terminal groups (as in monofunctional monomers), thealcohol only requires one —OH group. In the instance of linking groups(as in linear or branched multifunctional monomers), the alcoholrequires at least two —OH groups

It is also envisioned that the multifunctional monomers may be endcappedby transesterification with a methylene beta-ketoester group such as thegroup defined below

wherein L and R4 are as defined herein.In still another aspect, the invention provides a method for making amultifunctional methylene malonate monomer. The method comprises:

-   -   (a) reacting a sufficient amount of at least one first methylene        malonate monomer with a sufficient amount of a diol, a polyol or        a polymeric resin having at least two hydroxyl groups in the        presence of a catalyst, under suitable reaction conditions and        sufficient time, to form a reaction complex; and    -   (b) recovering multifunctional methylene malonate monomer from        the reaction complex.

In certain embodiments, the reacting step (a) is performed at roomtemperature and at atmospheric pressure. In other embodiments, thereacting step (a) is performed at elevated temperature and atatmospheric pressure. In still other embodiments, the reacting step (a)is performed at room temperature and under vacuum. In yet otherembodiments, the reacting step (a) is performed at elevated temperatureand under vacuum.

In yet another aspect, the invention provides a method of making amultifunctional beta-ketoester monomer comprising:

-   -   (a) reacting a sufficient amount of at least one first methylene        beta-ketoester monomer with a sufficient amount of a diol, a        polyol or a polymeric resin having at least two hydroxyl groups        in the presence of a catalyst, under suitable reaction        conditions and sufficient time, to form a reaction complex;    -   (b) recovering multifunctional methylene beta-ketoester monomer        from the reaction complex.

In still another aspect, the invention provides a method of making amultifunctional methylene malonate monomer comprising:

-   -   (a) reacting a malonic acid ester or a malonic acid chloride        with a diol, a polyol, or a polymeric resin comprising at least        two hydroxyl groups to form a multifunctional malonic acid        ester;    -   (b) reacting the multifunctional malonic acid ester formed in        step (a) with a source of formaldehyde; optionally in the        presence of an acidic or basic catalyst; and optionally in the        presence of an acidic or non-acidic solvent; and optionally in        the presence of an acid scavenger to form a reaction complex;        and    -   (c) recovering multifunctional methylene malonate monomer from        the reaction complex.        Reactants

In an exemplary embodiment, the Knoevenagel reaction for makingmultifunctional monomers as disclosed herein includes at least threebasic reactants: a malonic acid ester or malonic acid chlorides, alinking group donor (including —OH functional groups) and a source offormaldehyde.

The malonic acid esters or chlorides may be derived or obtained from anysource, including any commercial source, derived from nature, othercompounds, synthesized by other processes, etc. In certain embodiments,the malonic acid esters are obtained from “green” sources. For example,the malonic acid esters or chlorides can be derived from biologicalsources, such as via fermentation production systems wherebymicroorganisms generate the malonic acid esters is direct metabolicby-products of fermentation—or whereby the microorganisms generatemetabolic by-products of fermentation that can be then convertedinexpensively to the desired malonic acid esters. These fermentationproduction systems are well-known in the art and may utilize either—orboth—microorganisms derived from nature or engineered microorganismsthat are specifically designed to produce the desired malonic acid esterproducts, e.g., recombinant or engineered Escherichia coli.

Further reference to the methods, materials and procedures for preparingand/or obtaining monofunctional, difunctional and multifunctionalmalonic acids and/or malonic acid chlorides can be found in U.S. Pat.No. 7,663,000 (Quinoneimines of malonic acid diamides); U.S. Pat. No.7,553,989 (Malonic acid monoesters and process for producing the same);U.S. Pat. No. 7,208,621 (Malonic acid monomethyl derivatives andproduction process thereof); U.S. Pat. No. 7,109,369 (Malonic acidmonomethyl derivatives and production process thereof); U.S. Pat. No.6,794,365 (Malonic acid derivatives, processes for their preparationtheir use and pharmaceutical compositions containing them); U.S. Pat.No. 6,673,957 (Method for producing alkoxy malonic acid dinitriles);U.S. Pat. No. 6,613,934 (Enantiomerically enriched malonic acidmonoesters substituted by a tertiary hydrocarbon radical, and theirpreparation); U.S. Pat. No. 6,559,264 (Malonic acid ester/triazole mixedblocked HDI trimer/formaldehyde stabilization); U.S. Pat. No. 6,395,931(Malonic acid and esters thereof); U.S. Pat. No. 6,395,737 (Malonic acidderivatives, processes for their preparation, for their use andpharmaceutical compositions containing them); U.S. Pat. No. 6,284,915(Process for preparing 2-amino malonic acid derivatives and2-amino-1,3-propanediol derivatives, and intermediates for preparing thesame); U.S. Pat. No. 6,238,896 (Process for producing malonic acidderivatives); U.S. Pat. No. 5,886,219 (Process for preparing malonicacid and alkylmalonic acids); U.S. Pat. No. 5,817,870 (Process for theproduction of malonic acid or a salt thereof); U.S. Pat. No. 5,817,742(Polymer-conjugated malonic acid derivatives and their use asmedicaments and diagnostic agents); U.S. Pat. No. 5,693,621 (Malonicacid derivatives having antiadhesive properties); U.S. Pat. No.5,426,203 (Platinum complexes of malonic acid derivatives and processfor the preparation thereof); U.S. Pat. No. 5,334,747 (Method ofpreparing substituted malonic ester anilides and malonic acidmono-anilides); U.S. Pat. No. 5,292,937 (Use of malonic acid derivativecompounds for retarding plant growth); U.S. Pat. No. 5,210,222 (Processfor the production of malonic acid anhydride); U.S. Pat. No. 5,162,545(Malonic acid dyes and polycondensation products thereof); U.S. Pat. No.5,039,720 (Aqueous electrophoretic enamel coating materials, which canbe deposited at the cathode crosslinked with methane tricarboxylic acidamides of malonic acid derivatives); U.S. Pat. No. 5,021,486 (Hinderedamine-substituted malonic acid derivatives of s-triazine); U.S. Pat. No.4,914,226 (Malonic acid derivatives and methods for their synthesis);U.S. Pat. No. 4,835,153 (Malonic acid derivatives); U.S. Pat. No.4,736,056 (Process for the production of malonic acid derivativecompounds); U.S. Pat. No. 4,698,333 (Use of substituted malonic acidderivatives as agents for combating pests); U.S. Pat. No. 4,578,503(Alkylated or alkenylated malonic acid or its derivatives having afluorine); U.S. Pat. No. 4,556,649 (Substituted malonic acid diamideinsecticides, compositions and use); U.S. Pat. No. 4,539,423 (Processfor preparing diesters of malonic acid); U.S. Pat. No. 4,517,105(Metalworking lubricant composition containing a novel substitutedmalonic acid diester); U.S. Pat. No. 4,504,658 (Epimerization of malonicacid esters); U.S. Pat. No. 4,444,928 (Polymeric malonic acidderivatives); U.S. Pat. No. 4,443,624 (Method of preparing malonic aciddialkyl esters); U.S. Pat. No. 4,399,300 (Method of preparing malonicacid dialkyl esters); U.S. Pat. No. 4,329,479 (Process for producing1,3-dithiol-2-ylidene malonic acid dialkyl esters); U.S. Pat. No.4,256,908 (Process for preparing diesters of malonic acid); U.S. Pat.No. 4,237,297 (Piperidine containing malonic acid derivatives); U.S.Pat. No. 4,198,334 (Substituted malonic acid derivatives and their useas stabilizers); U.S. Pat. No. 4,154,914 (Process for producing acrylicrubber by copolymerizing acrylic ester and malonic acid derivativehaving active methylene group); U.S. Pat. No. 4,105,688 (Process for theproduction of malonic acid dinitrile and purification thereof); U.S.Pat. No. 4,102,809 (Malonic acid composition for thermoparticulatingcoating); U.S. Pat. No. 4,079,058 (Process of performing cyclizationreactions using benzyl or pyridylamino malonic acid derivatives); U.S.Pat. No. 4,046,943 (Malonic acid derivative composition for formingthermoparticulating coating); U.S. Pat. No. 4,036,985 (Mono substitutedmalonic acid diamides and process of preparing them); U.S. Pat. No.3,995,489 (Malonic acid derivative composition for formingthermoparticulating coating); U.S. Pat. No. 3,936,486 (Process for theproduction of malonic acid dinitrile), each of which are incorporated byreference in their entireties by reference herein.

The methods of the invention also contemplate any suitable source offormaldehyde. For example, the formaldehyde may be synthesized, derivedfrom another chemical species (e.g., paraformaldehyde), or obtained fromnature or from some other suitable source. In certain embodiments, theformaldehyde is introduced in the form of a gas. In certain embodiments,the formaldehyde is obtained from paraformaldehyde. Commercial sourcesof formaldehyde and paraformaldehyde are readily available, which mayinclude, for example, trioxane and formalin (e.g., aqueousformaldehyde). In other exemplary embodiments, formaldehyde may bereleased in another reaction or process and made available for theprocesses disclosed herein.

The transesterification reaction for making multifunctional methylenemalonates of the invention includes at least two basic reactants: amonofunctional methylene malonate monomer or monofunctional methylenebeta-ketoester monomer and a linking group donor (including —OHfunctional groups).

The methods of the invention contemplate any suitable source ofmonofunctional methylene malonate monomer. Further reference to themethods, materials and procedures for preparing and/or obtainingmonofunctional methylene malonate monomers can be found in U.S. PatentDocuments: U.S. Pat. Nos. 2,313,501; 2,330,033; 3,221,745; 3,523,097;3,557,185; 3,758,550; 3,975,422; 4,049,698; 4,056,543; 4,160,864;4,931,584; 5,142,098; 5,550,172; 6,106,807; 6,211,273; 6,245,933;6,420,468; 6,440,461; 6,512,023; 6,610,078; 6,699,928; 6,750,298; andPatent Publications 2004/0076601; WO/2012/054616A2; WO2012/054633A2.

In particular embodiments, the monofunctional methylene malonate monomercan be prepared according to the methods of the PCT InternationalApplications filed Oct. 19, 2011, claiming priority to U.S. ProvisionalApplication Ser. Nos. 61/405,029, filed Oct. 20, 2010, 61/405,033, filedOct. 20, 2010, 61/405,049, filed Oct. 20, 2010, 61/405,056, filed Oct.20, 2010, 61/405,078, filed Oct. 20, 2010, 61/523,311, filed Aug. 13,2011, and 61/523,705, filed Aug. 15, 2011, the entire contents each ofwhich are incorporated herein by reference in their entireties.

The methods of the invention also contemplate any suitable source ofterminal or linking group donors. Such donors include any materialhaving a reactive —OH group including oligomeric and polymeric alcohols,and alcohols which would results in polybutadienyl terminal or linkinggroups, a polyethylene glycol terminal or linking groups, a polyetherterminal or linking groups, a polyurethane terminal or linking groups,an epoxy terminal or linking groups, a polyacrylic terminal or linkinggroups, or a polycarbonate terminal or linking groups. Such alcohols maybe small molecules (linear or branched), polymeric, oligomeric, orresinous. In the instance of terminal groups (as in monofunctionalmonomers), the alcohol only requires one —OH group. In the instance oflinking groups (as in linear or branched multifunctional monomers), thealcohol requires at least two —OH groups

In certain embodiments, the source of the linking group may be straightor branched alcohols having two or more hydroxyl groups, polymericresins comprising two or more hydroxyl groups, represented by[A]-(OH)_(n) wherein:

[A] represents —(CR^(A)R^(B))_(n)—,—(CR^(A)R^(B))_(n)—O(C═O)—(CH₂)₁₋₁₅—(C═O)O—(CR^(A)R^(B))_(n)—,—(CH₂)_(n)—[CY]—(CH₂)_(n), a polybutadienyl linking group, apolyethylene glycol linking group, a polyether linking group, apolyurethane linking group, an epoxy linking group, a polyacryliclinking group, or a polycarbonate linking group;

each instance of R^(A) or R^(B) is independently H, C₁-C₁₅ alkyl, C₂-C₁₅alkenyl, a moiety represented by the formula:

wherein:

-   -   L is a linking group selected from the group consisting of        alkylene, alkenylene, haloalkylene, cycloalkylene,        cycloalkylene, heterocyclylene, heterocyclyl alkylene,        aryl-alkylene, heteroarylene or heteroaryl-(alkylene), or        alkoxy-(alkylene), each of which may be optionally branched and        each of which may be optionally substituted by alkyl, haloalkyl,        cycloalkyl, halo cycloalkyl, heterocyclyl, heterocyclyl-(alkyl),        aryl, aryl-(alkyl), heteroaryl, C₁-C₁₅ alkoxy, C₁-C₁₅ alkylthio,        hydroxyl, nitro, azido, cyano, acyloxy, carboxy, ester, each of        which may be optionally branched;    -   R³ is independently selected from C₁-C₁₅ alkyl, C₂-C₁₅ alkenyl,        halo-(C₁-C₁₅ alkyl), C₃-C₆ cycloalkyl, halo-(C₃-C₆ cycloalkyl),        heterocyclyl, heterocyclyl-(C₁-C₁₅ alkyl), aryl, aryl-(C1-C15        alkyl), heteroaryl or heteroaryl-(C₁-C₁₅ alkyl), or alkoxy        —(C1-15 alkyl), each of which may be optionally substituted by        C₁-C₁₅ alkyl, halo-(C₁-C₁₅ alkyl), C₃-C₆ cycloalkyl, halo-(C₃-C₆        cycloalkyl), heterocyclyl, heterocyclyl-(C₁-C₁₅ alkyl), aryl,        aryl —(C₁-C₁₅ alkyl), heteroaryl, C₁-C₁₅ alkoxy, C₁-C₁₅        alkylthio, hydroxyl, nitro, azido, cyano, acyloxy, carboxy, or        ester; and    -   R⁴ is alkyl, alkenyl, haloalkyl, cycloalkyl, halo cycloalkyl,        heterocyclyl, heterocyclyl alkyl), aryl-(alkyl), heteroaryl or        heteroaryl-(alkyl), or alkoxy-(alkyl), each of which may be        optionally branched and each of which may be optionally        substituted by alkyl, haloalkyl), cycloalkyl, halo cycloalkyl,        heterocyclyl, heterocyclyl-(alkyl), aryl, aryl-(alkyl),        heteroaryl, C₁-C₁₅ alkoxy, C₁-C₁₅ alkylthio, hydroxyl, nitro,        azido, cyano, acyloxy, carboxy, ester, each of which may be        optionally branched;

[CY] represents an alkyl, alkenyl, haloalkyl, cycloalkyl, halocycloalkyl, heterocyclyl, heterocyclyl alkyl), aryl-(alkyl), heteroarylor heteroaryl-(alkyl), or alkoxy-(alkyl) group;

each instance of n is independently an integer from 1 to 25; and

each instance of Q represents —O— or a direct bond.

By way of illustration only, and not by means of limitation, in certainembodiments the linking group source is a diol, such as ethylene diol,1,3-propylene diol, 1,2propylene diol, 1-4-butanediol, 1,2-butane diol,1,3-butane diol, 2,3-butane diol, or 1,5-pentane diol. In otherembodiments, the linking group is a triol, such as 1,2,3-propane triol,1,2,3-butane triol, or 1,2,4-butane triol. Specific experimentalexamples are provided below.

Catalysts

Certain embodiments contemplate the use of any suitable acidic or basiccatalyst. In certain preferred aspects, it has been surprisingly foundthat no catalyst at all is required to conduct the reaction.

In certain embodiments, catalysts that are typically used forKnoevenagel reactions with formaldehyde to make monofunctional methylenemalonate monomers are contemplated. Such catalysts include, for example,basic catalyst salts, such as, potassium acetate and the neutralco-catalyst copper acetate.

Certain other embodiments contemplate catalysts that heretofore werepreviously unused in the context of the Knoevenagel reaction withformaldehyde to synthesize monofunctional monomers. Such catalystsinclude various acidic, basic, neutral, or even amphoteric catalysts.

Acidic catalysts can include, for example, lithium chloride, borontrifluoride etherate, ferric sulfate, zirconium oxychloride, cupricchloride, titanium tetrachloride, zinc chloride, aluminum oxide, or zincoxide. Accordingly, the acidic catalysts of the invention may include,but are not limited to, paratoluene sulfonic acid, dodecylbenzenesulfonic acid, borontrifluoride, zinc perchlorate, sulfated zirconiumoxide, sulfated titanium oxide, lithium chloride, boron trifluorideetherate, ferric sulfate, zirconium oxychloride, cupric chloride,titanium tetrachloride, and zinc chloride. In certain embodiments, theacidic catalyst may include, but is not limited to, Para TolueneSulfonic Acid (PTSA), Dodecyl Benzene Sulfonic Acid (DBSA), Amberlyst15, BF3, Zinc Perchlorate, Zirconium Oxide-Sulfated, or TitaniumOxide-Sulfated.

Neutral catalysts can also include silica and other insolublesurface-active agents.

In certain other embodiments, the methods disclosed herein utilize abasic catalyst. Basic catalysts of the invention may include, but arenot limited to, potassium acetate, sodium acetate, zinc acetate, zincacetate dihydrate, aluminum acetate, calcium acetate, magnesium acetate,magnesium oxide, copper acetate, lithium acetate, aluminum oxide, andzinc oxide.

In still further embodiments, the amphoteric catalysts can include, butare not limited to, aluminum oxide, aluminum acetate, zinc acetate,magnesium acetate, and zinc oxide.

In still other embodiments, particularly the transesterificationschemes, an enzymatic catalyst is utilized. Such enzymatic catalystsinclude, but are not limited to Novozym 435.

In still other embodiments, the inventive methods utilize a polymericcatalyst. Such polymeric catalysts include, but are not limited to Dowex2, Dowex 4, Dowex 5, and Nafion.

In still other embodiments, the present inventors have surprisingly andunexpectedly found that no catalyst is required to conduct the synthesisreaction of the invention. Specifically, in this embodiment, thereaction can be conducted with all of the reactants added to thereaction vessel at the start of the reaction prior to adding heat. Thisreaction surprisingly can be run rapidly and in a continuous mode andunexpectedly avoids the formation of—or substantially minimizes theformation of—deleterious side products, unwanted polymerizationcomplexes and degradation of the monomer products.

Recovery

Embodiments disclosed herein contemplate any suitable method forrecovery or isolation of the multifunctional monomer products from thereaction complex. In certain embodiments of the present invention, therecovery method includes filtering an enzymatic catalyst, and use ofdistillation techniques. In certain other embodiments, the recovery orisolation method involves one or more rounds of a rapid distillation ofa condensed vapor phase method, e.g., flash distillation or superheatdistillation. In still other embodiments, the recovery or isolationmethod involves liquid chromatographic separation of multifunctionalmonomer products. In yet other embodiments, the recovery method involvesgas chromatographic separation of vaporized multifunctional methylenemalonate products directly from the vapor phase.

Those having ordinary skill in the art will appreciate that simpledistillation methods are well known. Simple distillation is a widelyused method for separating the components of a liquid mixture, e.g.,reaction mixture of the present invention, and depends upon thedifferences in the ease of vaporization of the components. Typically,the most volatile components of the liquid mixture will vaporize at thelowest temperature, whereas the least volatile components will vaporizeat higher temperatures. The vaporized components pass through a cooledtube or condenser causing the components to condense back into theirliquid states and deposited in a collector or equivalent vessel. Byseparating the distillated into sequentially collected fractions rangingfrom most volatile to least volatile components, the components can beseparated. The process can be repeated on any given fraction(s) tofurther separate the components.

In certain exemplary embodiments disclosed herein, the reaction includesexcess monofunctional monomer reactant that must be separated from themultifunctional monomer product. Typically, however, the desiredmultifunctional monomer product is less volatile than the startingreactant. Thus, it is envisioned that use of distillation as aseparation technique would result in the monomer reactant being drivenoff first, with the product remaining behind, thus requiring furtherseparation techniques.

Those having skill in the art may employ any separation techniques asrequired to isolate and/or recover the desired multifunctional monomerproduct. Further, separation and recovery techniques may be used incombination where suitable as known by those having skill in the art.

Compositions

The multifunctional monomers disclosed herein can be incorporated intoany number of compositions and products. Certain exemplary formulatedcompositions may be utilized as adhesives, sealants, coatingcompositions, inks, paints, and the like. Additionally, polymerizablecompositions contemplated herein may be utilized to form polymer-basedproducts such as coatings (e.g., thermal barrier coatings), paint,textile fibers, water-treatment polymers, ink carriers, paint carriers,packaging film, moldings, medical polymers, a polymer film, a polymerfiber, a polymer sheet, and so on. It is envisioned that polymerizablecompositions contemplated herein may be utilized as matrix material forcomposites (wood, fiber, carbon, polymeric) and even be utilized in thefiller material.

Embodiments disclosed herein may be formulated to include one or morematerials to extend the shelf-life of polymerizable compositions as wellas control the onset of cure of the materials. In certain embodiments,the compositions are formulated such that the composition is stable forat least 1 month, or for at least 2 months, or for at least 3 months, orfor at least 4 months, or for at least 5 months, or for at least 5-10months, or for at least 10-20 months, or for at least 20-30 months.Preferably, adhesive compositions comprising the multifunctionalmonomers of the invention, or other commercial compositions or products,are stable for at least one year.

Such formulation materials include acidic stabilizer, volatile acidstabilizers, acidic gases, free radical stabilizers, sequesteringagents, cure accelerators and rheology modifiers.

The present invention contemplates any suitable acidic stabilizer knownin the art, including, for example, trifluoromethane sulfonic acid,maleic acid, methane sulfonic acid, difluoro acetic acid,trichloroacetic acid, phosphoric acid, dichloroacetic acid,chlorodifluoro or like acid. Acidic stabilizers can include any materialwhich can be added to the monomer or polymerizable compositions toextend shelf-life, e.g., by up to, for example, 1 year or more. Suchacidic stabilizers may have a pKa in the range of, for example, betweenabout −15 to about 5, or between about −15 to about 3, or between about−15 to about 1, or between −2 to about between about −2 to about 2, orbetween about 2 to about 5, or between about 3 to about 5.

Volatile acid stabilizers include any material which can be added to themonomer or polymerizable compositions to extend shelf-life and stabilizethe vapor phase above the composition upon storage, e.g., acidic gases.Such volatile acid stabilizers may have a boiling point, for example,less than about 200° C.; less than about 170° C.; or less than about130° C.

Acidic gases include any gaseous material which can be added to themonomer or polymerizable compositions to extend shelf-life and stabilizethe vapor phase above the composition upon storage. Such acid gases caninclude, but are not limited to, SO₂ or BF₃.

For each of these acidic stabilizing materials, such acidic stabilizercan be present in a concentration of about 0.1 ppm to about 100 ppm;about 0.1 ppm to about 25 ppm; or about 0.1 ppm to about 15 ppm.

Free radical stabilizers can include any material capable of stabilizingor inhibiting free radical polymerization of the material upon standing.In one embodiment, the free radical stabilizers are phenolic freeradical stabilizers such as, HQ (hydroquinone), MEHQ(methyl-hydroquinone), BHT (butylated hydroxytoluene) and BHA (butylatedhydroxyanisole). In certain embodiments, the free radical stabilizersare present in a concentration of 0.1 ppm to 10,000 ppm; 0.1 ppm to 3000ppm; or 0.1 ppm to 1500 ppm. In certain other embodiments, particularlywhere a free radical or ultraviolet cure will be utilized on thematerials of the invention, the free radical stabilizers are present ina concentration of 0.1 ppm to 1000 ppm; 0.1 ppm to 300 ppm; or 0.1 ppmto 150 ppm.

Sequestering agents include any material capable of enhancing thebonding of materials containing acid salts such as paper or wood. Suchsequestering agents include, but are not limited to crown ethers, silylcrowns, calixarenes and polyethylene glycols. Sequestering agents alsoenhance the utility of surface accelerators that are acid salts appliedto surfaces to control the rate of cure of the materials.

Cure accelerators include any material capable of speeding the rate ofcure of the multifunctional monomers of the invention. Cure acceleratorsalso include any material capable of speeding the cure through volume ofthe multifunctional monomers of the invention. Such cure acceleratorsinclude but are not limited to sodium or potassium acetate; acrylic,maleic or other acid salts of sodium, potassium lithium copper andcolbalt; salts such as tetrabutyl ammonium fluoride, chloride, orhydroxide; or chemically basic materials such as amines and amides, orsalts of polymer bond acids, or of benzoate salts, 2,4-pentanedionatesalts, sorbate salts, or propionate salts. Such cure accelerators can beadded directly to the compositions of the invention or applied to thematerial to be bonded prior to addition of the composition of theinvention.

Rheology modifiers include any material which can modify the viscosityof the compositions of the invention as well as thixotropic propertiesfor greater utility in certain applications. Rheology modifiers include,but are not limited to, hydroxyethylcellulose, ethylhydroxyethylcellulose, methylcellulose, polymeric thickeners, pyrogenicsilica or a combination thereof.

In certain embodiments, the compositions may include tougheners. Suchtougheners include, but are not limited to, acrylic rubbers; polyesterurethanes; ethylene-vinyl acetates; fluorinated rubbers;isoprene-acrylonitrile polymers; chlorosulfonated polyethylenes;homopolymers of polyvinyl acetate; and reaction products of thecombination of ethylene, methyl acrylate and monomers having carboxylicacid cure sites, which once formed are then substantially free ofprocessing aids and anti-oxidants; and combinations thereof. In certainembodiments, the tougheners include those disclosed in U.S. Pat. No.4,440,910 (O'Connor), directed to rubber toughened cyanoacrylatecompositions through the use of certain organic polymers as tougheningadditives that are elastomeric, i.e., rubbery, in nature, such asacrylic rubbers; polyester urethanes; ethylene-vinyl acetates;fluorinated rubbers; isoprene-acrylonitrile polymers; chlorosulfonatedpolyethylenes; and homopolymers of polyvinyl acetate. In certainembodiments, the toughener is an elastomeric polymer which is acopolymer of methyl acrylate and ethylene, manufactured by DuPont, underthe name of VAMAC, such as VAMAC N123 and VAMAC B-124. VAMAC N123 andVAMAC B-124 are reported by DuPont to be a master batch ofethylene/acrylic elastomer. In other embodiments, the toughener may bethe DuPont materials called VAMAC B-124, N123, VAMAC G, VAMAC VMX 1012or VCD 6200. In other instances, the toughener may be a rubbertoughening component having (a) reaction products of the combination ofethylene, methyl acrylate and monomers having carboxylic acid curesites, (b) dipolymers of ethylene and methyl acrylate, and combinationsof (a) and (b), which once the reaction products and/or dipolymers areformed are then substantially free of processing aids, such as therelease agents octadecyl amine (reported by DuPont to be availablecommercially from Akzo Nobel under the tradename ARMEEN 18D), complexorganic phosphate esters (reported by DuPont to be availablecommercially from R.T. Vanderbilt Co., Inc. under the tradename VANFREVAM), stearic acid and/or polyethylene glycol ether wax, andanti-oxidants, such as substituted diphenyl amine (reported by DuPont tobe available commercially from Uniroyal Chemical under the tradenameNAUGARD 445). Commercial examples of such rubber tougheners includeVAMAC VMX 1012 and VCD 6200 rubbers, and these may also be used.

The polymerizable compositions contemplated herein may also optionallyinclude other additives, such as plasticizing agents, thixotropicagents, natural or synthetic rubbers, filler agents, and reinforcingagents, etc. Such additives are well known to those skilled in the art.

The polymerizable compositions of the invention may optionally includeat least one plasticizing agent that imparts flexibility to the polymerformed from the multifunctional monomers. The plasticizing agentpreferably contains little or no moisture and should not significantlyaffect the stability or polymerization of the monomer. Such plasticizersare useful in polymerizable compositions to be used in any applicationin which flexibility of the adhesive or polymer product is desirable.

Examples of suitable plasticizers include, without limitation, acetyltributyl citrate, dimethyl sebacate, triethyl phosphate,tri(2-ethylhexyl)phosphate, tri(p-cresyl) phosphate, glyceryltriacetate, glyceryl tributyrate, diethyl sebacate, dioctyl adipate,isopropyl myristate, butyl stearate, lauric acid, trioctyl trimellitate,dioctyl glutarate, and mixtures thereof. Preferred plasticizers aretributyl citrate and acetyl tributyl citrate. In embodiments, suitableplasticizers include polymeric plasticizers, such as polyethylene glycol(PEG) esters and capped PEG esters or ethers, polyester gluterates andpolyester adipates.

The addition of plasticizing agents in amounts less than about 60 weight%, or less than about 50 weight %, or less than about 30 weight %, orless than about 10 weight %, or less than about 5 weight %, or less thanabout 1 weight % or less, provides increased film strength (e.g.,toughness) of the polymerized material over polymerized materials nothaving such plasticizing agents.

The polymerizable compositions disclosed herein may also optionallyinclude at least one thixotropic agent, i.e., the property of exhibitinga high fluidity during deformation by force of a sprayer, roller ortrowel, but losing the fluidity when left at rest. Suitable thixotropicagents are known to the skilled artisan and include, but are not limitedto, silica gels such as those treated with a silyl isocyanate. Examplesof suitable thixotropic agents are disclosed in, for example, U.S. Pat.No. 4,720,513 or 4,510,273, the disclosures of which are herebyincorporated in their entireties.

The polymerizable compositions disclosed herein may also optionallyinclude at least one natural or synthetic rubber to impart impactresistance, which is preferable especially for industrial compositionsof the present invention. Suitable rubbers are known to the skilledartisan. Such rubbers include, but are not limited to, dienes, styrenes,acrylonitriles, and mixtures thereof. Examples of suitable rubbers aredisclosed in, for example, U.S. Pat. Nos. 4,313,865 and 4,560,723, thedisclosures of which are hereby incorporated in their entireties.

The polymerizable compositions disclosed herein may also optionallycomprise one or more other reinforcing agents (e.g., fibrousreinforcements) other than natural or synthetic rubber to impart impactresistance and/or to impart structural strength or to provide shape orform. Examples of such agents are well known in the art. Examples ofsuitable fibrous reinforcement include PGA microfibrils, collagenmicrofibrils, cellulosic microfibrils, and olefinic microfibrils. Thecompositions may also contain colorants such as dyes, pigments, andpigment dyes. Examples of suitable colorants include6-hydroxy-5-[(4-sulfophenyl)axo]-2-naphthalene-sulfonic acid (FD+CYellow No. 6);9-(o-carboxyphenoyl)-6-hydroxy-2,4,5,7-tetraiodo-3H-xanthen-3-onemonohydrate (FD+C Red No. 3); and2-(1,3-dihydro-3-oxo-5-sulfo-2H-indol-2-ylidene)-2,3-dihydro-3-oxo-1H-indole-5-sulfonic acid (FD+C Blue No. 2), wherein the suitable colorantshould not destabilize the monomer.

The polymerizable compositions disclosed herein may also optionallyinclude at least one thickening agent. Suitable thickeners include, forexample, polycyanoacrylates, polylactic acid, poly-1,4-dioxa-2-one,polyoxalates, polyglycolic acid, lactic-glycolic acid copolymers,polycaprolactone, lactic acid-caprolactone copolymers,poly-3-hydroxybutyric acid, polyorthoesters, polyalkyl acrylates,copolymers of alkylacrylate and vinyl acetate, polyalkyl methacrylates,and copolymers of alkyl methacrylates and butadiene. Examples of alkylmethacrylates and acrylates are poly(2-ethylhexyl methacrylate) andpoly(2-ethylhexyl acrylate), also poly(butylmethacrylate) andpoly(butylacrylate), also copolymers of various acrylate andmethacrylate monomers, such aspoly(butylmethacrylate-co-methylacrylate).

To improve the cohesive strength of adhesives formed from thepolymerizable compositions disclosed herein, difunctional monomericcross-linking agents may be added to the monomer compositions of thisinvention. Such crosslinking agents are known. U.S. Pat. No. 3,940,362to Overhults, which is hereby incorporated in its entirety by reference,discloses such crosslinking agents.

Other compositions and additives contemplated for use in compositionsdisclosed herein include additional stabilizers, accelerators,plasticizers, fillers, ° pacifiers, inhibitors, thixotrophy conferringagents, dyes, fluorescence markers, thermal degradation reducers,adhesion promoters, thermal resistance conferring agents andcombinations thereof, and the like, some of which are exemplified byU.S. Pat. Nos. 5,624,669; 5,582,834; 5,575,997; 5,514,371; 5,514,372;5,312,864 and 5,259,835, the disclosures of all of which are herebyincorporated in their entirety by reference.

Depending on whether the material is a monomer-based composition (e.g.,inks, adhesives, coatings, sealants or reactive molding) or apolymer-based composition (e.g., fibers, films, sheets, medicalpolymers, composite polymers and surfactants), one having ordinary skillin the art will have the knowledge and skill by which to formulate suchcompositions and/or products without undue experimentation havingsuitable amounts, levels and combinations of the above types ofadditives and components.

EXAMPLES

The structures, materials, compositions, and methods described hereinare intended to be representative examples of the invention, and it willbe understood that the scope of the invention is not limited by thescope of the examples. Those skilled in the art will recognize that theinvention may be practiced with variations on the disclosed structures,materials, compositions and methods, and such variations are regarded aswithin the ambit of the invention.

The following examples illustrate various exemplary embodiments of themethods described in this disclosure.

Analytical Methods

The structures of monomers of this invention were confirmed using one ormore of the following procedures.

NMR

In certain instances, routine one-dimensional NMR spectroscopy wasperformed on either a 400 MHz Varian® spectrometer or a 400 MHz Bruker®spectrometer. The samples were dissolved in deuterated solvents.Chemical shifts were recorded on the ppm scale and were referenced tothe appropriate solvent signals, such as 2.49 ppm for DMSO-d6, 1.93 ppmfor CD3CN, 3.30 ppm for CD3OD, 5.32 ppm for CD2C12 and 7.26 ppm forCDC13 for 1H spectra.

In other certain instances, routine NMR spectroscopy was performed on a300 MHz Bruker NMR spectrometer. Samples were dissolved in deuteratedchloroform and were referenced to the solvent peak at 7.26 ppm. Asneeded, an internal standard of hexamethyldisiloxane (HMDS) was addedfor absolute quantitation. 1H NMR was used for certain samples, with 13CNMR, DEPT-135, and two-dimensional HSQC (Heteronuclear Single QuantumCorrelation) spectroscopy used as needed to validate structures. HMDSappears at 0.06 ppm in the 1H spectrum and at 1.94 in the 13C spectrum.

GC/MS

In certain embodiments, electron impact mass spectra (EI-MS) wereobtained with a Hewlett Packard 5970 mass spectrometer equipped HewlettPackard 5890 Gas Chromatograph with. The ion source was maintained at270° C.

For certain other embodiments, structural characterization of themultifunctional monomers, were obtained using two types of massspectrometry techniques. The first technique used is electrosprayionization (ESI) which is coupled with both ion trap (IT) and Fouriertransform ion cyclotron resonance (FT-ICR) mass analyzers. ESI is a softionization technique where ions are produced directly from the liquidphase. In this analysis, formic acid was added to a diluted solution ofDEMM multifunctional monomer in acetonitrile, thus producing positivelycharged or protonated molecular ions. These ions are directly measuredin the FT-ICR mass analyzer. Mass measurement in the FT-ICR cell isextremely accurate because it is the frequency of the ion cyclotronmotion of the excited ions that is measured. Frequency can be measuredvery accurately and is directly proportional to mass/charge ratio. Theion trap mass analyzer is used here for MSn analysis. In the ion trap,collision induced dissociation is used to fragment the molecular ions sothat structural information can be obtained. These fragment ions canalso be measured very accurately in the FT-ICR cell.

Electrospray Ionization Mass Spectrometry (ESI/MS)

Electrospray ionization mass spectra were obtained using a ThermoLTQ-FT, a hybrid instrument consisting of a linear ion trap massanalyzer and a Fourier transform ion cyclotron resonance (FT-ICR) massanalyzer. MS/MS spectra were obtained in the ion trap by collision withhelium at a normalized collision energy of 25. Accurate massmeasurements were obtained from the FT-ICR scans.

Abbreviations and Acronyms

A comprehensive list of the abbreviations used by organic chemists ofordinary skill in the art appears in The ACS Style Guide (third edition)or the Guidelines for Authors for the Journal of Organic Chemistry. Theabbreviations contained in said lists, and all abbreviations utilized byorganic chemists of ordinary skill in the art are hereby incorporated byreference. For purposes of this invention, the chemical elements areidentified in accordance with the Periodic Table of the Elements, CASversion, Handbook of Chemistry and Physics, 67th Ed., 1986-87.

More specifically, when the following abbreviations are used throughoutthis disclosure, they have the following meanings:

-   -   atm atmosphere    -   br s broad singlet    -   C Celsius    -   d doublet    -   dd doublet of doublets    -   MM methylene malonate    -   HQ hydroquinone    -   GC-MS Gas Chromatograph mass spectroscopy    -   g gram    -   h hour, hours    -   1H NMR proton nuclear magnetic resonance    -   J coupling constant (NMR spectroscopy)    -   L liter    -   M mol L-1 (molar)    -   m multiplet    -   MHz megahertz    -   min minute, minutes    -   mL milliliter    -   mM micromolar    -   mol mole    -   MS mass spectrum, mass spectrometry    -   m/z mass-to-charge ratio    -   N equivalents L-1 (normal)    -   NMR Nuclear Magnetic Resonance    -   pH negative logarithm of hydrogen ion concentration    -   q quartet    -   rt room temperature    -   singlet    -   t triplet        General Methodology. Transesterification Reaction

Investigations were made to provide multifunctional monomers (e.g.,methylene malonates and methylene beta-ketoesters) via atransesterification process. Multifunctional monomers provideopportunities to cross-link, for enhanced physical properties, and tofunctionalize the molecules for wider applicability.

The general experiment procedure is outlined below:

-   -   1) Follow reasonable safety precautions such as working in a        functioning fume hood, review and follow safety data sheet        recommendations, exercise appropriate caution when working with        liquid nitrogen, use personal protective equipment, exercise        caution when handling hot glassware.    -   2) Unless otherwise specified, test and measurement conditions        are:        -   a. Procedure 1:            -   i. ˜55° C.            -   ii. ˜50 torr vacuum        -   b. Procedure 2:            -   i. ˜70° C.            -   ii. ˜100 torr vacuum    -   3) Procedure:        -   a. Clean and dry an appropriately sized round bottom flask.        -   b. Add catalyst (e.g., Novazym 435) to the flask at 20            weight percent of the volume of starting material (e.g.,            diethyl methylene malonate DEMM); an appropriate amount of            starting material (e.g., DEMM), and an appropriate amount of            OH-containing linking group (e.g., diol, polyol, polymeric            resin, etc). For a diol, the starting material is added at            5× molar ratio of diol to ensure adequate stoichiometric            amounts plus desired excess.        -   c. Provide appropriate stir mechanisms, vacuum set up and            collection apparatuses.        -   d. Heat the reaction vessel, under vacuum, and under gentle            agitation. Vacuum is utilized to pull off alcohol generated            as a side product.        -   e. Collect reaction samples at appropriate time intervals to            monitor progress of the reaction (e.g., 4 hours, 6 hours, 8            hours). Stabilize the reaction complex with a suitable            stabilizer. (Samples were initially analyzed with H-NMR and            TLC to show product formation.)        -   f. Transfer reaction complex to a non-reactive bottle (e.g.,            HDPE) while filtering the catalyst.        -   g. Employ suitable separation techniques to isolate and            remove reaction product (e.g., multifunctional monomer) from            excess starting material (e.g., DEMM).    -   4) Results and Analysis:

Unless otherwise specified, the diethyl methylene malonate (DEMM)starting material in the reactions discussed below contained a smallamount of diethyl malonate (DEM) as an impurity. Both DEM and DEMM areable to participate in the transesterification reaction. The malonateCH₂ appears at 3.3 ppm in the 1H NMR and at 41 ppm in the 13C NMRspectra. The carbonyl for the malonate appears at 166 ppm. These peakscan be seen in all spectra of these mixtures.

DEMM:

DEM:

For NMR analysis, samples were diluted in deuterated chloroform prior to¹H NMR spectroscopy at 300 MHz (Bruker). A more concentrated sample wasalso prepared in a solution of 0.01 M Cr(acac)₃ in deuterated chloroformand was analyzed by quantitative ¹³C NMR spectroscopy at 75 MHz.

Example 1 Reaction of DEMM and 1,6-hexanediol (HD) byTransesterification

The reaction scheme disclosed herein was performed using DEMM and1,6-hexanediol. The following monomer was obtained.

NMR: The ¹H NMR spectrum is shown in FIG. 1. Peak assignments areannotated. Free 1,6-hexanediol shows a peak at 3.6 ppm. The NMR spectrumshows essentially complete consumption of the hexanediol. The broadfeature at 2.5 ppm is due to some loss of the double bond during thereaction. The ¹³C NMR spectrum (bottom) and the DEPT-135 spectrum (top)are shown in FIG. 2. Free 1,6-hexane diol would have a peak at 63 ppm.The ester is clearly shown at 65 ppm. The NMR spectra support theproposed structure, although extended structures cannot be ruled out(i.e., higher order oligomers).

ESI/MS: A 1:20000 dilution of the DEMM-1,6-hexanediol multifunctional inacetonitrile with 1% formic acid was directly infused into theelectrospray source. The masses of the protonated ions and theircorresponding relative intensities for the DEMM-1,6-hexanediolmultifunctional synthesis product are shown in FIGS. 14 and 15. FIGS. 14and 15 are the same sample but differ in the mass range scanned. Themajor ions present and the elemental formulas of these ions are listedin Table 1.

TABLE 1 Ions detected in the ESI/MS analysis of DEMM-1,6-hexanediolmultifunctional and the corresponding elemental formula and massmeasurement error. Accurate Mass Measurement (m/z) Error (ppm) ElementalFormula 173.08088 0.256 [C₈H₁₂O₄ + H]⁺ 195.06284 0.306 [C₈H₁₂O₄ + Na]⁺359.17014 0.267 [C₁₇H₂₆O₈ + H]⁺ 371.17015 0.285 [C₁₈H₂₆O₈ + H]⁺393.15209 0.230 [C₁₈H₂₆O₈ + Na]⁺ 417.21203 0.290 [C₂₀H₃₂O₉ + H]⁺439.19395 0.195 [C₂₀H₃₂O₉ + Na]⁺ 545.25934 0.160 [C₂₆H₄₀O₁₂ + H]⁺557.25940 0.264 [C₂₇H₄₀O₁₂ + H]⁺ 569.25942 0.293 [C₂₈H₄₀O₁₂ + H]⁺591.24139 0.307 [C₂₈H₄₀O₁₂ + Na]⁺ 615.30129 0.280 [C₃₀H₄₆O₁₃ + H]⁺755.34862 0.208 [C₃₇H₅₄O₁₆ + H]⁺ 767.34870 0.309 [C₃₈H₅₄O₁₆ + H]⁺813.39055 0.237 [C₄₀H₆₀O₁₇ + H]⁺

The ions detected are the ions formed from the addition of a hydrogenfrom the acid or from the addition of sodium from the surroundingsolvent or environment. The ion at m/z 173 represents the protonatedunreacted DEMM which is expected to be present because DEMM was used inexcess during the synthesis of the DEMM-1,6-hexanediol product. Thesodium adduct of the DEMM is the ion present at m/z 195. The ion at m/z371 is the most abundant ion present and corresponds to the protonatedmolecular ion of the DEMM-1,6-hexanediol product with the structureshown below. The sodium adduct for this molecule is also present at m/z393. Present as a minor ion at m/z 359, is the multifunctional withoutthe methylene group.

Another minor species present at m/z 417 is the result of the additionof one ethanol across the methylene double bond as shown below. Thesodium adduct of the molecule is also detected at m/z 439.

The molecular ion at m/z 569 represents the higher orderDEMM-1,6-hexanediol multifunctional product represented below and is thesecond most abundant ion in FIG. 14. The sodium adduct of this higherorder multifunctional is also present at m/z 591. Other ions present atm/z 545 and m/z 557 can be attributed to the presence of themultifunctional present missing two and one methylene groups,respectively.

The protonated molecular ion for an even higher order multifunctional isfound at m/z 767. The minor ion at m/z 755 can be attributed to the lackof one methylene group within this higher order structure.

Example 2 Reaction of DEMM and Cyclohexanedimethanol (CHDM) byTransesterification

The reaction scheme disclosed herein was performed using DEMM andcyclohexanedimethanol. The following monomer was obtained.

NMR: The cyclohexanedimethanol used was a mixture of cis and trans,which means that the NMR spectrum of the starting material shows twosets of peaks. FIG. 3 is the ¹H NMR spectrum of the reaction product.Unreacted starting material would show up very close to the malonateimpurity at 3.3-3.4 ppm. However, it is clear that most of the alcoholhas reacted. The ¹³C and DEPT-135 spectra are shown in FIG. 4 and forcomparison, an overlay of the reaction product and an Aldrich libraryspectrum of the cyclohexanedimethanol starting material are shown inFIG. 5. The shift of the starting material is consistent with theproduct shown above. Again, NMR would not be able to easily rule out thepresence of higher order oligomers.

Example 3 Reaction of DEMM and Poly-Tetrahydrofuran (Poly-THF) byTransesterification

The reaction scheme disclosed herein was performed using DEMM andpoly-tetrahydrofuran. The following monomer was obtained.

NMR: The poly(THF) starting material used has an average molecularweight of 250, which corresponds to an average repeat unit of n=3. The¹H NMR spectrum is shown in FIG. 6. Unreacted alcohol groups wouldappear at 3.6 ppm, but this is also where the ether peaks will show up,making it difficult to discern the structure from this spectrum.

The ¹³C NMR and DEPT-135 spectra are shown in FIG. 7. The peak at 65 ppmis due to the ester. Unreacted alcohol would appear at 62 ppm, veryclose to the ethyl ester peak. However, a quantitative ¹³C NMRexperiment shows very little extra area of the 62 ppm peak vs. the 14ppm peak of the ethyl, indicating very little unreacted alcohol present,supporting the structure shown above.

Example 4 Reaction of DEMM and 1,8-octanediol by Transesterification

The reaction scheme disclosed herein was performed using DEMM and1,8-octanediol. The following monomer was obtained.

The 1H NMR spectrum (FIG. 8) and the 13C NMR and DEPT-135 spectra (FIG.9) show evidence of complete transesterification of the diol with theDEMM. The double bond (peaks at 6.4 ppm in the 1H and at 134 and 135 ppmin the 13C spectra) is also intact.

Example 5 Reaction of DEMM and 1,10-decanediol by Transesterification

The reaction scheme disclosed herein was performed using DEMM and1,8-octanediol. The following monomer was obtained.

The 1H NMR spectrum (FIG. 10) and the 13C NMR and DEPT-135 spectra (FIG.11) show evidence of complete transesterification of the diol with theDEMM. The double bond (peaks at 6.4 ppm in the 1H and at 134 and 135 ppmin the 13C spectra) is also intact.

Example 6 Reaction of DEMM and Trimethylolpropane by Transesterification

The reaction scheme disclosed herein was performed using DEMM andtrimethylolpropane. The following monomer was obtained.

The ¹H NMR spectrum is shown in FIG. 12. This spectrum is morecomplicated. While there is some intact double bond left at 6.4 ppm, thepeaks in the 2.4-2.8 ppm range are likely due to polymerization of thedouble bond. The ¹³C and DEPT-135 NMR spectra are shown in FIG. 13. Thepeak at 133.5 ppm (CH₂) and the peak at 135 ppm (quaternary) support thegeminal double bond. The peak at 68 ppm is the esterified TMP and thepeak at 66 ppm is due to the unreacted TMP alcohols. Other peaks presentare likely due to side reactions (Michael Addition by the alcohols).

Example 7 Reaction of DEMM and 1,3-benzene Dimethanol byTransesterification

The reaction scheme disclosed herein is performed using appropriatereactant to obtain the following monomers:

The ¹H NMR spectra are shown in FIGS. 16 and 17. The peaks in the5.0-5.3 ppm region are consistent with the transesterification. There issome double bond left intact at 6.5 ppm. However, the peaks between 2.4and 2.9 ppm are likely caused by polymerization of the double bond. The4-hour reaction (FIG. 16) shows more intact double bond than the 8-hourreaction (FIG. 17).

Example 8 Reaction of DEMM and Poly(Butadiene) Hydroxyl Terminated byTransesterification

The reaction scheme disclosed herein can be performed usingpoly(butadiene) hydroxyl terminated as a starting material:

One exemplary product formed by the transesterification of DEMM withpoly(butadiene) hydroxyl terminated may be represented as:

Example 9 Additional Examples

The reaction schemes disclosed herein may also be performed using thefollowing starting materials: a polyester or oligomer/polymer containingone or more ester groups in a linear or cyclic structure, including, butnot limited to, polybutyl succinate, polyethylene adipate,polycaprolactone (made from cyclic caprolactone). In such instances,functionality which would interfere with the transesterificationcatalysts of cause instability in the final product containing methylenemalonate functionality should be avoided.

The resulting methylene malonate functionality can be terminal or withinthe overall molecular structure. Such materials can be copolymers withfor example styrene, acrylonitrile, ethers, and ketones that containsufficient ester functionality to allow ester interchange.

Equivalents

Those skilled in the art will recognize, or be able to ascertain usingno more than routine experimentation, many equivalents to the specificembodiments of the invention described herein. Such equivalents areintended to be encompassed by this invention.

What is claimed is:
 1. A method of making a multifunctional methylenemalonate monomer comprising: (a) reacting at least one methylenemalonate monomer with a diol, a polyol or a polymeric resin having atleast two hydroxyl groups in the presence of an enzymatic catalyst toform a reaction complex wherein the at least one methylene malonatemonomer is provided in an excess amount with respect to the diol, polyolor polymeric resin having at least two hydroxyl groups; and (b)recovering multifunctional methylene malonate monomer comprising morethan one methylene malonate core formula linked by the diol, polyol orpolymeric resin having at least two hydroxyl groups from the reactioncomplex; (c) adding a stabilizer to the reaction complex formed in step(a); wherein in step (a) the at least one methylene malonate monomer isprovided in an excess amount with respect to the diol, polyol orpolymeric resin having at least two hydroxyl groups, recoveringmultifunctional methylene malonate monomer in step (b) includesseparating the multifunctional methylene malonate monomer from theexcess methylene malonate monomer and the diol, polyol or polymericresin having at least two hydroxyl groups; and the diol, polyol orpolymeric resin having at least two hydroxyl groups correspond to theformula (HO)-[A]-(OH)_(m) wherein: [A] is independently selected from—(CR^(A)R^(B))_(n)—,—(CR^(A)R^(B))_(n)—O(C═O)—(CH₂)₁₋₁₅—(C═O)O—(CR^(A)R^(B))_(n)—,—(CH₂)_(n)—[CY]—(CH₂)_(n), a polybutadienyl linking group, apolyethylene glycol linking group, a polyether linking group, apolyurethane linking group, an epoxy linking group, a polyacryliclinking group, or a polycarbonate linking group; each instance of R^(A)or R^(B) is independently selected from H, C₁-C₁₅ alkyl, a moietycorresponding to the formula:

wherein: L is a linking group selected from the group consisting ofalkylene, haloalkylene, cycloalkylene, cycloalkylene, oralkoxy-(alkylene), each of which may be optionally branched and each ofwhich may be optionally substituted by alkyl, haloalkyl, C₁-C₁₅ alkoxy,each of which may be optionally branched; R³ is independently selectedfrom C₁-C₁₅ alkyl, C₂-C₁₅ alkenyl, halo-(C₁-C₁₅ alkyl), C₃-C₆cycloalkyl, halo-(C₃-C₆ cycloalkyl), or alkoxy —(C₁₋₁₅ alkyl), each ofwhich may be optionally substituted by C₁-C₁₅ alkyl, halo-(C₁-C₁₅alkyl), and CY is independently selected from an alkyl, alkenyl,haloalkyl, cycloalkyl, halo cycloalkyl, or alkoxy -(alkyl) group; andeach instance of m and n are independently an integer from 1 to
 25. 2.The method according to claim 1, wherein the reaction conditions in step(a) comprise room temperature and atmospheric pressure; elevatedtemperature and atmospheric pressure; room temperature and under vacuum;elevated temperature and under vacuum; or any combination thereof. 3.The method according to claim 2, wherein step (a) is performed at anelevated temperature between about 40° C. and 85° C.
 4. The methodaccording to claim 1, wherein step (a) comprises removing alcohol thatis formed.
 5. The method according to claim 1, wherein the methylenemalonate is reacted with the diol or polyol of C₁-C₁₂ alkyl diol, anyisomer of cyclohexane dimethanol, polybutyl THF, or trimethylolpropane.6. The method according to claim 1, wherein step (a) is performed undervacuum conditions.
 7. The method according to claim 1, wherein themultifunctional monomers correspond to the formula:

wherein: each instance of R¹ and R² are independently selected fromC₁-C₁₅ alkyl, C₂-C₁₅ alkenyl, halo-(C₁-C₁₅ alkyl), C₃-C₆ cycloalkyl,halo-(C₃-C₆ cycloalkyl), or alkoxy —(C₁₋₁₅ alkyl), each of which may beoptionally substituted by C₁-C₁₅ alkyl, halo-(C₁-C₁₅ alkyl), C₃-C₆cycloalkyl, halo-(C₃-C₆ cycloalkyl), or C₁-C₁₅ alkoxy; [A] isindependently selected from —(CR^(A)R^(B))_(n)—,—(CR^(A)R^(B))_(n)—O(C═O)—(CH₂)₁₋₁₅—(C═O)O—(CR^(A)R^(B))_(n)—,—(CH₂)_(n)—[CY]—(CH₂)_(n), a polybutadienyl linking group, apolyethylene glycol linking group, a polyether linking group, apolyurethane linking group, an epoxy linking group, a polyacryliclinking group, or a polycarbonate linking group; each instance of R^(A)or R^(B) is independently selected from H, C₁-C₁₅ alkyl, each instanceof m is independently an integer from 1 to 25; and; Q is O.
 8. Themethod according to claim 7, wherein [A] is a linking group derived fromC₁-C₁₂ alkyl diol, any isomer of cyclohexane dimethanol, polybutyl THF,or trimethylolpropane.
 9. The method according to claim 7, wherein [A]is C₁-C₁₅ alkyl, or C₃-C₆ cycloalkyl.
 10. The method according to claim1 wherein an excess of at least one methylene malonate monomer isreacted with a diol, a polyol or a polymeric resin having at least twohydroxyl groups in the absence of a solvent.
 11. The method according toclaim 1 wherein an acidic stabilizer having a pKa of from −15 to 5 isadded at a concentration of about 0.1 to about 100 ppm and a phenolicfree radical stabilizer is added at a concentration of about 0.1 toabout 10,000.
 12. The method according to claim 1 wherein the stabilizeris one or more acidic stabilizers, volatile acid stabilizers, or freeradical stabilizers.
 13. A method of making a multifunctional methylenemalonate monomer comprising: (a) reacting at least one methylenemalonate monomer having disubstituted vinyl functionality with a diol, apolyol or a polymeric resin having at least two hydroxyl groups andwhich does not have functional groups that react with the disubstitutedvinyl functionality on the methylene malonate monomer, in the presenceof an enzymatic catalyst to form a reaction complex; wherein the atleast one methylene malonate monomer is provided in an excess amountwith respect to the diol, polyol or polymeric resin having at least twohydroxyl groups; and (b) recovering multifunctional methylene malonatemonomer comprising more than one methylene malonate core formula linkedby the diol, polyol or polymeric resin having at least two hydroxylgroups from the reaction complex, (c) adding a stabilizer to thereaction complex formed in step (a); recovering multifunctionalmethylene malonate monomer in step (b) includes separating themultifunctional methylene malonate monomer from the excess methylenemalonate monomer and the diol, polyol or polymeric resin having at leasttwo hydroxyl groups.
 14. The method according to claim 13 wherein thediol, the polyol or the polymeric resin having at least two hydroxylgroups is independently an oligomeric alcohol or polymeric alcohol. 15.The method according to claim 13 wherein the at least one methylenemalonate monomer is contacted with the polymeric resin having at leasttwo hydroxyl groups.
 16. The method according to claim 15 wherein the atleast one methylene malonate monomer is contacted with the polymericresin having at least two hydroxyl groups which is independently apolybutadienyl, polyethylene glycol, polyether, a polyurethane, epoxy,polyacrylic, or polycarbonate polymeric resin having at least twohydroxyl groups.
 17. The method according to claim 13 wherein the atleast one methylene malonate monomer is contacted with the polyolcomprising a triol.
 18. The method according to claim 17 wherein thetriol is 1,2,3-propane triol, 1,2,3 butane triol or 1,2,4 butane triol.19. The method according to claim 12, wherein the acidic stabilizer istrifluoromethane sulfonic acid, maleic acid, methane sulfonic acid,difluoro acetic acid, trichloroacetic acid, phosphoric acid,dichloroacetic acid, chlorodifluoro acid, hydroquinone,methylhydroquinone, butylated hydroxytoluene, or butylatedhydroxyanisole.
 20. The method according to claim 12, wherein in step(c), the acidic stabilizer is added to the reaction complex inconcentrations of about 0.1 ppm to about 100 ppm of the reactioncomplex.